Download Molecular Dynamics Investigation of Biomimetic Antifreeze Macromolecules Sarah-Jane Richards

Molecular Dynamics
Investigation of Biomimetic
Antifreeze Macromolecules
Sarah-Jane Richards
Supervised by Dr. Rebecca Notman
What is the Scientific importance of
the project?
• Cryopreservation of biological materials.
• Blood cell, stem cells and even whole
organs1.
- Traditionally - Glycerol or DMSO2
- Very expensive, large concentrations
• Alternatively Antifreeze glycoproteins
1. Nutt, D. R.; Smith, J. C., J. Am. Chem. Soc., 2008, 130, 13066
2. Matsumura, K.; Hyon, S.-H., 2009, 30, 4842.
What are Antifreeze Glycoproteins and
Why are they Important?
• Prevent polar fish from freezing in Antarctic
conditions1.
1. Matsumura, K.; Hyon, S.-H., Biomaterials, 2009, 30, 4842.
What are the antifreeze properties
they show?
• Thermal Hysteresis1
• Dynamic Ice Shaping2
• Recrystallisation Inhibition1
• Potential Cryopreservant
1. Gibson, M. I., Polym. Chem., 2010, 1, 8, 1141
2. Tachibana, Y.; Fletcher, G. L.; Fujitani, N.; Tsuda, S.; Monde, K.; Nishimura, S-I.,
Angew. Chem. Int. Ed. 2004, 43, 856-856.
Why are glycoproteins not currently
used?
• Difficulties with obtaining them from natural
sources1
• Challenges of total synthesis2
1. Tachibana, Y.; Fletcher, G. L.; Fujitani, N.; Tsuda, S.; Monde, K.; Nishimura, SI., Angew. Chem. Int. Ed. 2004, 43, 856-856.
2. Heggemann, C.; Budke, C.; Schomburg, B.; Majer, Z.; Wiβbrock, M.; Koop, T.;
Sewald, N., Amino Acids, 2010, 38, 213.
How has this been overcome?
• Mimics of AFGPs1,2
• Gibson Lab have been synthesising
glycotripeptides
• However, their mechanism of action is
unknown.
• Aim: To use Molecular Dynamics to help
elucidate mechanism of action
1. Gibson, M. I.; Barker, C. A.; Spain, S. G. et al., Biomacromolecules, 2009, 10, 2, 328.
2. Tam, R. Y.; Rowley, C. N.; Petrov, I.; Zhang, T.; Afagh, N. A.; Woo, T. K.; Ben, R. N., J.
Am. Chem. Soc., 2009, 131, 15745
Why are Molecular Dynamics
simulations important?
• They can help elucidate the mechanism of
action.
• They can suggest a conformation of these
peptides.
• Help design and optimise biomimetic
polymers.
What have I been simulating?
• 4 sugar functionalised peptides.
• Effect of number of hydroxyl groups
• Stereochemistry
How did I go about the simulations?
• All-atom model
• Introducing the monosaccharides
• TIP4P/ICE
• NPT simulations for 100 ns at two
temperatures
• Analysis - Cluster Analysis
- Hydrogen Bonding
- Solvent Accessible Surface Area
Cluster Analysis
298 K
267 K
Hydrogen Bonding Analysis
Water 298 K 0.804 ± 0.0002 H-bonds
Water 267 K 0.847 ± 0.0002 H-bonds
Ice 267 K 1.000 ± 0.0002 H-bonds
Solvent Accessible Surface Area
298 K
267 K
Solvent Accessible Surface Area
298 K
267 K
Solvent Accessible Surface Area
298 K
267 K
Further Cluster Analysis
298 K
267 K
Further Cluster Analysis
298 K
267 K
Further Cluster Analysis
298 K
267 K
Further Cluster Analysis
298 K
267 K
What can we conclude from these
results?
Acknowledgements
• Thank you to Becky and Matt for putting the
project together.
• Thanks to Becky for her support throughout
the project.
• Thanks to Sang and Anthony for making the
write-up room a bit more interesting.
Thank you for
listening!